Bone tissue constantly undergoes the coupled processes of bone formation by osteoblasts and bone resorption by osteoclasts termed remodeling. Bone mass is increased when bone formation exceeds bone resorption. Osteoporosis is a common skeletal disorder affecting nearly 20 million Americans mostly over the age of 45 adversely effecting the dynamic bone remodeling process and resulting in 1.2 million fractures annually [S. L. Bonnick, J. Am. Med. Women's Assoc., 45 75 (1990)]. It is thought to be caused by an imbalance between bone resorption and bone formation such that there is a net loss of bone and reduction in bone mineral density. Several kinds of osteoporosis are recognized: senile (due to aging), postmenopausal (due to estrogen-depletion following menopause), disuse (due to immobilization) and steroid-induced. Current treatments focus on preventing the bone loss with calcitonin, estrogen or bisphosphonates, ensuring an adequate supply of calcium to the bone with vitamin D and calcium or attempting to stimulate bone formation with fluoride. As formation of bone is "coupled" to previous resorption of bone, preventing bone loss can itself result in a small increase in bone mass (approx. 5%) due to the filling of resorption cavities by osteoblasts in the absence of any loss of bone elsewhere in the skeleton, a point which needs to be borne in mind when interpreting clinical data.
Estrogen replacement therapy has been the treatment of choice in women. To be effective in preventing osteoporosis it may need to be taken for 5 to 10 years [Christiansen, C. and Lindsay R. "Estrogens, bone loss and preservation." Osteoporosis International 1990; 1:15-21] and this presents compliance problems and is further associated with increased risk of certain types of cancers. Treatment with sodium fluoride which is mitogenic for osteoblasts may result in bone density increase up to 8-10% a year. However, significant side-effects have also been reported, and the bone growth is irregular and fracture incidence does not appear to be significantly lowered. The class of drugs currently under development are the bisphosphonates. Treatment with these organic phosphates produces a sustained increase in bone mass for several years, but some side effects that occur are renal failure, hypotension and extra-skeletal calcification. Thus none of the present treatments are entirely suitable for the treatment of osteoporosis.